Until now cell culture gel materials may be isolated from natural sources or completely synthetic. Gels such as collagen, which produce inherently lamellar structures, are incapable of forming complex 3D networks in isolation. Gels such as those derived from EHS mouse sarcoma cells resemble the extra cellular environment found in tissues much better than pure collagen and also provide three dimensional environment within which cells may grow and assemble in to complex architectures. Naturally derived gelators are difficult to fully characterise and require intensive batch to batch analysis to achieve this characterisation, biologically derived gels suffer from inherent variability, risk of contamination and pathogen transfer along with excessive price premiums. For many research groups, additional trace contamination such as unwanted growth factors inherently present in biologically sourced materials are unacceptable experimental interferences and are unacceptable for use in-vivo. At the other end of the spectrum, synthetically derived gels such as those derived from poly(N-isopropylacrylamide) co-polymers exhibit low cell viability and cell differentiation ability, which requires additional mixtures of bioactives such as glucocorticoids and transforming growth factor beta (TGF-β). The use of synthetic gelators largely removes the natural variation found in biological gelators, but concomitantly eliminates the inherent biological activity of natural gels. The ability to eliminate the biological variability whilst retaining biological activity is a challenge not yet fully realised.
The ability to harvest complex biological systems formed in these gels also remains a challenge. Traditionally cells must be released from biological surfaces by the use of tripsin or for the gel to be mechanically dissolved or manually removed from the surface of the structure.
Gelatable structures demonstrated above are not universal in nature and cannot be easily applied in a minimally invasive way in-vivo. Some examples of themoresponsive materials that can be applied in a minimally invasive manner through a cooled catheter exist, such as those disclosed in US 2010/0215731 A1. However these materials suffer from the same drawbacks as described above resulting in poor cell viability.
Mechanically the properties of all of the biologically derived gels are dictated by the non-covalent interactions of the peptide subunits. The result is that the pore size and mechanical strength are relatively fixed. The mechanical properties and nature of the cross links are even more so fixed in the case of the synthetically derived gels.
WO 2011/007012 discloses a hydrogel comprising oligo(alkylene glycol) functionalized polyisocyanopeptides. The polyisocyanopeptides are prepared by functionalizing an isocyanopeptide with oligo-(alkylene glycol) side chains and subsequently polymerizing the oligo-alkylene glycol functionalized isocyanopeptides. WO2011/007012 suggests use of the hydrogels for tissue engineering or neuron regeneration.
Although the known cell cultures are satisfactory for some applications, there is an increased need in the art for cell cultures which can be used in a wide range of situations.